Incremental value of copeptin to highly sensitive cardiac Troponin I for rapid rule-out of myocardial infarction

The incremental value of copeptin, a novel marker of endogenous stress, for rapid rule-out of non-ST-elevation myocardial infarction (NSTEMI) is unclear when sensitive or even high-sensitivity cardiac troponin cTn (hs-cTn) assays are used.In an international multicenter study we evaluated 1929 consecutive patients with symptoms suggestive of acute myocardial infarction (AMI). Measurements of copeptin, three sensitive and three hs-cTn assays were performed at presentation in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists using all clinical information including coronary angiography and levels of hs-cTnT. The incremental value in the diagnosis of NSTEMI was quantified using four outcome measures: area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI), sensitivity and negative predictive value (NPV). Early presenters (< 4h since chest pain onset) were a pre-defined subgroup.NSTEMI was the adjudicated final diagnosis in 358 (18.6%) patients. As compared to the use of cTn alone, copeptin significantly increased AUC for two (33%) and IDI (between 0.010 and 0.041 (all p < 0.01)), sensitivity and NPV for all six cTn assays (100%); NPV to 96-99% when the 99 th percentile of the respective cTnI assay was combined with a copeptin level of 9 pmol/l (all p < 0.01). The incremental value in early presenters was similar to that of the overall cohort.When used for rapid rule-out of NSTEM in combination with sensitive or hs-cTnI assays, copeptin provides a numerically small, but statistically and likely also clinically significant incremental value

One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I

We aimed to prospectively derive and validate a novel 1h-algorithm using high-sensitivity cardiac troponin I (hs-cTnI) for early rule-out and rule-in of acute myocardial infarction.; We performed a prospective multicenter diagnostic study enrolling 1811 patients with suspected acute myocardial infarction. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data, and serial measurements of hs-cTnT (but not hs-cTnI). The hs-cTnI 1h-algorithm, incorporating measurements performed at baseline and absolute changes within 1 hour, was derived in a randomly selected sample of 906 patients (derivation cohort), and then validated in the remaining 905 patients (validation cohort).; Acute myocardial infarction was the final diagnosis in 18% of patients. After applying the hs-cTnI 1h-algorithm developed in the derivation cohort to the validation cohort, 50.5% of patients could be classified as "rule-out," 19% as "rule-in," 30.5% as "observe." In the validation cohort, the negative predictive value for acute myocardial infarction in the "rule-out" zone was 99.6% (95% confidence interval, 98.4%-100%), and the positive predictive value for acute myocardial infarction in the "rule-in" zone was 73.9% (95% confidence interval, 66.7%-80.2%). Negative predictive value of the 1h-algorithm was higher compared with the classical dichotomous interpretation of hs-cTnI and to the standard of care combining hs-cTnI with the electrocardiogram (both P > .001). Positive predictive value also was higher compared with the standard of care (P > .001).; Using a simple algorithm incorporating baseline hs-cTnI values and the absolute change within the first hour allows safe rule-out as well as accurate rule-in of acute myocardial infarction in 70% of patients presenting with suspected acute myocardial infarction

Misdiagnosis of myocardial infarction related to limitations of the current regulatory approach to define clinical decision values for cardiac troponin

Misdiagnosis of acute myocardial infarction (AMI) may significantly harm patients and may result from inappropriate clinical decision values (CDVs) for cardiac troponin (cTn) owing to limitations in the current regulatory process.In an international, prospective, multicenter study, we quantified the incidence of inconsistencies in the diagnosis of AMI using fully characterized and clinically available high-sensitivity (hs) cTn assays (hs-cTnI, Abbott; hs-cTnT, Roche) among 2300 consecutive patients with suspected AMI. We hypothesized that the approved CDVs for the 2 assays are not biologically equivalent and might therefore contribute to inconsistencies in the diagnosis of AMI. Findings were validated by use of sex-specific CDVs and parallel measurements of other hs-cTnI assays. AMI was the adjudicated diagnosis in 473 patients (21%). Among these, 86 patients (18.2%) had inconsistent diagnoses when the approved uniform CDV was used. When sex-specific CDVs were used, 14.1% of female and 22.7% of male AMI patients had inconsistent diagnoses. Using biologically equivalent CDV reduced inconsistencies to 10% (

Early rule-out and rule-in of myocardial infarction using sensitive cardiac Troponin I

It is currently unknown, whether and to what extent sensitive cardiac troponin (s-cTn) allows shortening of the time required for safe rule-out and rule-in of acute myocardial infarction (AMI).We aimed to develop and validate early rule-out and rule-in algorithms for AMI using a thoroughly-examined and commonly used s-cTnI assay in a prospective multicenter study including 2173 patients presenting to the emergency department with suspected AMI. S-cTnI was measured in a blinded fashion at 0 h, 1 h, and 2 h. The final diagnosis was centrally adjudicated by two independent cardiologists. In the derivation cohort (n = 1496), we developed 1h- and 2h-algorithms assigning patients to "rule-out", "rule-in", or "observe". The algorithms were then prospectively validated in the validation cohort (n = 677).AMI was the adjudicated diagnosis in 17% of patients. After applying the s-cTnI 1h-algorithm developed in the derivation cohort to the validation cohort, 65% of patients were classified as "rule-out", 12% as "rule-in", and 23% to "observe". The negative predictive value for AMI in the "rule-out" group was 98.6% (95% CI, 96.9-99.5), the positive predictive value for AMI in the "rule-in" group 76.3% (95% CI, 65.4-85.1). Overall, 30-day mortality was 0.2% in the "rule-out" group, 1.0% in the "observe" group, and 3.0% in the "rule-in" group. Similar results were obtained for the 2h-algorithm.When used in conjunction with other clinical information including the ECG, a simple algorithm incorporating s-cTnI values at presentation and after 1h (or 2h) will allow safe rule-out and accurate rule-in of AMI in the majority of patients

Safety and efficacy of the 0 h/3 h protocol for rapid rule out of myocardial infarction

The early and accurate diagnosis of acute myocardial infarction (AMI) is an important medical and economic challenge. We aimed to prospectively evaluate the performance of the new European Society of Cardiology rapid 0-hour/3-hour (0 h/3 h) rule out protocol for AMI.We enrolled 2,727 consecutive patients presenting with suspected AMI without persistent ST-segment elevation to the emergency department in a prospective international multicenter study. The final diagnosis was adjudicated by 2 independent cardiologists. The performance of the 0 h/3 h rule out protocol was evaluated using 4 high-sensitivity (primary analysis) and 3 sensitive cardiac troponin (cTn) assays.Acute myocardial infarction was the final diagnosis in 473 patients (17.3%). Using the 4 high-sensitivity cTn assays, the 0-hour rule out protocol correctly ruled out 99.8% (95% [confidence interval] CI, 98.7%-100%), 99.6% (95% CI, 98.5%-99.9%), 100% (95% CI, 97.9%-100%), and 100% (95% CI, 98.0%-100%) of late presenters (>6 h from chest pain onset). The 3-hour rule out protocol correctly ruled out 99.9% (95% CI, 99.1%-100%), 99.5% (95% CI, 98.3%-99.9%), 100% (95% CI, 98.1%-100%), and 100% (95% CI, 98.2%-100%) of early presenters

Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay

We aimed to prospectively validate a novel 1-hour algorithm using high-sensitivity cardiac troponin T measurement for early rule-out and rule-in of acute myocardial infarction (MI).In a multicentre study, we enrolled 1320 patients presenting to the emergency department with suspected acute MI. The high-sensitivity cardiac troponin T 1-hour algorithm, incorporating baseline values as well as absolute changes within the first hour, was validated against the final diagnosis. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data and serial measurements of high-sensitivity cardiac troponin T levels.Acute MI was the final diagnosis in 17.3% of patients. With application of the high-sensitivity cardiac troponin T 1-hour algorithm, 786 (59.5%) patients were classified as "rule-out," 216 (16.4%) were classified as "rule-in" and 318 (24.1%) were classified to the "observational zone." The sensitivity and the negative predictive value for acute MI in the rule-out zone were 99.6% (95% confidence interval [CI] 97.6%-99.9%) and 99.9% (95% CI 99.3%-100%), respectively. The specificity and the positive predictive value for acute MI in the rule-in zone were 95.7% (95% CI 94.3%-96.8%) and 78.2% (95% CI 72.1%-83.6%), respectively. The 1-hour algorithm provided higher negative and positive predictive values than the standard interpretation of highsensitivity cardiac troponin T using a single cut-off level (both p < 0.05). Cumulative 30-day mortality was 0.0%, 1.6% and 1.9% in patients classified in the rule-out, observational and rule-in groups, respectively (p = 0.001).This rapid strategy incorporating high-sensitivity cardiac troponin T baseline values and absolute changes within the first hour substantially accelerated the management of suspected acute MI by allowing safe rule-out as well as accurate rule-in of acute MI in 3 out of 4 patients.ClinicalTrials.gov, NCT00470587